Injection device

ABSTRACT

An injection device includes a syringe with a hollow needle and a stopper for sealing the syringe and displacing a medicament stored in the syringe. An arrangement for transferring a translation of a drive means to a plunger for pushing against the stopper includes a release latch pivoted at one end and connected to either the drive means or the plunger. The other end of the release latch engages the other one of the drive means or the plunger. The non-pivoted end of the release latch disengages by rotation upon contact between a ramp and another component when the stopper has displaced most of a predefined medicament dose. The release latch is long enough to provide a clearance between the plunger and the drive means when engaged to allow the plunger, stopper and needle to be retracted inside the syringe or a housing after disengaging the release latch.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a U.S. National Phase Application pursuant to35 U.S.C. §371 of International Application No. PCT/EP2011/053157 filedMar. 3, 2011, which claims priority to European Patent Application No.10155948.2 filed on Mar. 9, 2010. The entire disclosure contents ofthese applications are herewith incorporated by reference into thepresent application.

FIELD OF INVENTION

The invention relates to an injection device.

BACKGROUND

Administering an injection is a process which presents a number of risksand challenges for users and healthcare professionals, both mental andphysical.

Injection devices (i.e. devices capable of delivering medicaments from amedication container) typically fall into two categories—manual devicesand auto-injectors.

In a manual device—the user must provide the mechanical energy to drivethe fluid through the needle. This is typically done by some form ofbutton/plunger that has to be continuously pressed by the user duringthe injection. There are numerous disadvantages to the user from thisapproach. If the user stops pressing the button/plunger then theinjection will also stop. This means that the user can deliver anunderdose if the device is not used properly (i.e. the plunger is notfully pressed to its end position). Injection forces may be too high forthe user, in particular if the patient is elderly or has dexterityproblems.

The extension of the button/plunger may be too great. Thus it can beinconvenient for the user to reach a fully extended button. Thecombination of injection force and button extension can causetrembling/shaking of the hand which in turn increases discomfort as theinserted needle moves.

Auto-injector devices aim to make self-administration of injectedtherapies easier for patients. Current therapies delivered by means ofself-administered injections include drugs for diabetes (both insulinand newer GLP-1 class drugs), migraine, hormone therapies,anticoagulants etc.

Auto-injectors are devices which completely or partially replaceactivities involved in parenteral drug delivery from standard syringes.These activities may include removal of a protective syringe cap,insertion of a needle into a patient's skin, injection of themedicament, removal of the needle, shielding of the needle andpreventing reuse of the device. This overcomes many of the disadvantagesof manual devices. Forces required of the user/button extension,hand-shaking and the likelihood of delivering an incomplete dose arereduced. Triggering may be performed by numerous means, for example atrigger button, the action of placing the autoinjector against the skinor the action of the needle reaching its injection depth. In somedevices the energy to deliver the fluid is provided by a spring.

Auto-injectors may be disposable or single use devices which may only beused to deliver one dose of medicament and which have to be disposed ofafter use. Other types of auto-injectors may be reusable. Usually theyare arranged to allow a user to load and unload a standard syringe. Thereusable auto-injector may be used to perform multiple parenteral drugdeliveries, whereas the syringe is disposed after having been spent andunloaded from the auto-injector. The syringe may be packaged withadditional parts to provide additional functionality.

US 2002/0095120 A1 discloses an automatic injection device whichautomatically injects a pre-measured quantity of fluid medicine when atension spring is released. The tension spring moves an ampoule and theinjection needle from a storage position to a deployed position when itis released. The content of the ampoule is thereafter expelled by thetension spring forcing a piston in a proximal direction inside theampoule. After the fluid medicine has been injected energy stored in thetension spring is released and the injection needle is automaticallyretracted back to its original storage position.

In order to prevent post-injection needle stick injuries, syringes withneedle retraction have been developed. These syringes comprise astopper, a plunger connected to the stopper, a hollow injection needleand a needle retraction spring. When the stopper in such a syringe hasbottomed out and displaced at least nearly all of the syringe's contentit grips a part of the needle protruding into the interior of thesyringe. The needle retraction spring pushes the plunger in distaldirection, i.e. away from the injection site. The plunger then pulls thestopper and the needle in distal direction until the needle is hiddeninside the syringe.

GB 2 447 339 A discloses an autoinjector comprising an outer housing inwhich is mounted a syringe comprising a barrel for holding a volume ofmedicament, a needle at one end of the barrel and a plungeraxially-moveable in the barrel, the autoinjector further comprising aninner housing intermediate the outer housing and the syringe and anenergy source in communication with said inner housing, wherein theinner housing is moveable by the energy source between three positions,namely a first position in which the inner housing is in communicationwith the barrel such that, in use, the plunger and barrel are moveableaxially so as to move at least part of said needle out of the outerhousing; a second position in which the inner housing is incommunication with the plunger but not the barrel such that, in use,said plunger is moveable axially into said barrel so as to expelmedicament through the needle; and a third position in which the innerhousing is in communication with neither the plunger nor the barrel suchthat, in use, the plunger and barrel are able to retract in order toretract the needle into the outer housing, characterised in that theplunger includes biasing means for axially biasing the barrel, beforeactivation of the energy source, to a position forward of the part ofthe inner housing which acts on the barrel in said first position.

US 2003/105430 A1 discloses an automatic injector in which the needle isinjected automatically into the injection site (e.g., a patient's skin),delivery is initiated upon activation of the injector, and the needle isretracted after the end of delivery. Preferably the needle is not seenby the user prior to, during or after injection. Prior to and afterinjection, the needle is withdrawn into the device so as to avoid anypotential injury or health risk to the user or health care provider. Theinjector includes a housing and a control unit arranged to slide withinthe housing to move a piston rod during drug delivery and to pivotwithin the housing for needle retraction. The injector may also includea back rod that moves the piston rod before activation of the injectorfor titration and reconstitution and automatically disengages from thepiston rod upon activation of the injector. A needle-locking device canbe used in any number of pen-like injectors or other types of injectorsor syringes. The needle-locking device includes a clip that insures thata needle assembly within an injector is in a locked position before andafter use.

SUMMARY

One object of the present invention to provide an injection device witha means for transferring a translation to a plunger of a syringearranged in the injection device and allowing the plunger to retractafter the end of an injection cycle.

This object is achieved by an injection device according to claim 1.

Preferred embodiments of the invention are given in the dependentclaims.

According to the invention an injection device comprises a syringe witha hollow needle and a stopper for sealing the syringe and displacing amedicament stored in the syringe, the injection device furthercomprising a drive means, a plunger arranged for pushing against thestopper and an arrangement for transferring a translation of the drivemeans to the plunger. The arrangement comprises an elongate releaselatch member. The release latch member is pivoted at one end which isconnected to either the drive means or the plunger. Another end of therelease latch member is arranged for engaging the respective other oneof the drive means or the plunger. The release latch member is arrangedto have its non-pivoted other end disengaged by rotation due to contactbetween at least one ramp and another component when the stopper has atleast nearly displaced all of a predefined dose of the medicament. Forcepropagation from the drive means to the plunger is thus interrupted so aneedle retraction spring may retract the needle. The ramp may bearranged at the release latch member or at another part moving relativeto the release latch member during the translation. The other componentmay be another ramp or a pin. A length of the release latch member isspecified so as to provide a clearance between the plunger and the drivemeans when the release latch member is engaged in order to allow atleast the plunger, the stopper and a hollow needle of the syringe to beretracted at least far enough to hide the needle inside the syringe orinside a housing after disengaging the release latch member.

If the arrangement is used with a so called needle retraction syringe,such as a Unilife® syringe, the needle is hidden inside the syringeafter delivery of the predefined dose. In this case it is sufficient toallow retraction of the plunger, the stopper, and the needle.

If a different syringe type with a fixed needle is used, the plunger andthe entire syringe along with the needle and the stopper have to beretracted so as to hide the needle inside the housing.

Preferably the release latch member is pivoted at the end connected tothe drive means. This allows for using standard syringes with needleretraction functionality without having to attach the release latchmember to their plunger. Instead the release latch member may be part ofa reusable injection device, e.g. an auto-injector containing areplaceable syringe.

The predefined dose of the medicament is preferably the entire contentof the syringe.

In one embodiment the release latch member is arranged to be disengageddepending on a distance travelled until at least the entire predefineddose has been delivered. This may be achieved by ramp engagement of therelease latch member to a housing or chassis which translated relativeto the release latch member and the plunger.

In a preferred embodiment the release latch member is arranged to bedisengaged depending on a time elapsed from a beginning of thetranslation. This may be achieved by a damper unit arranged in serieswith the drive means and the release latch member. The damper unit maycomprise a plunger spring and a viscous damper. The plunger spring isarranged for being compressed when subjected to the force of the drivemeans acting against a counteracting force of the stopper, which dependson friction between the stopper and the inner wall of the syringe and onthe hydrostatic resistance of the liquid medicament being displacedthrough the hollow needle. Compression of the plunger spring is delayedby the viscous damper. At the beginning of the translation the plungerspring is in an expanded state, but during the translation it is slowlycompressed. A coefficient of damping of the damper is specified suchthat a time taken to fully compress the plunger spring is greater than atime required to displace the predefined dose. The release latch membermay be pivoted in a proximal end of the damper unit, and arranged to berotated out of engagement with the plunger by a distal end of the damperunit when the plunger spring is fully compressed. Force propagation fromthe drive spring to the plunger is thus interrupted and the needleretraction spring may retract the needle. Provided the predefined doseis the entire content, both problems are solved, reliably retracting thehollow needle to a safe position and fully emptying the syringe which isparticularly desirable with expensive drugs. Emptying the syringe isalso important for dosage accuracy.

The function of the plunger spring is to reset the damper after use inorder to prepare it for another injection cycle. However, in a singleuse device the damper unit may be implemented without a plunger spring.

In the context of this specification the term proximal refers to thedirection pointing towards the patient during an injection while theterm distal refers to the opposite direction pointing away from thepatient.

Preferably, the viscous damper may comprise a piston fixed to a drivecollar by a connecting rod. The drive collar is arranged at a proximalend of the drive means. The piston has a greater diameter than theconnecting rod. A hollow cylinder with an internal diameter slightlygreater than the diameter of the piston may be arranged around thepiston thus allowing the piston and cylinder to reciprocate. A proximalend face of the cylinder may be fully closed and a distal end face ofthe cylinder may be arranged to seal the cylinder against the connectingrod. Thus, the interior of the cylinder may be divided into two separatecavities by the piston. At least one transfer port may be providedthrough the piston in a manner to allow a fluid to flow between thedistal side of the piston and the proximal side, i.e. from one cavityinto the other. The size and number of the transfer ports and theviscosity of the fluid in the cylinder determine the dampingcharacteristics of the viscous damper.

A gasket ring may be arranged to seal the piston against the cylinder inorder to avoid uncontrolled leaking of the fluid between the cavitieswhich might lead to less repeatable damping characteristics.

Another gasket ring may be arranged to seal the connecting rod againstthe distal end face of the cylinder in order to avoid fluid leaking outof the damper which would otherwise in a drift of the dampingcharacteristics due to disappearing liquid and to pollution of theinterior of the auto-injector. An air space may be provided in thecylinder, e.g. by only partially filling it with the damping fluid inorder to compensate for the volume of the connecting rod as it goes intothe cylinder. Otherwise the viscous damper could lock since the volumeof fluid displaced by the piston on its proximal side is greater thanthe volume increase on the distal side due to the volume of theconnecting rod. Air or another gas provided in the cylinder in additionto the viscous fluid can be compressed in order to compensate thisdisparity in volume change. A hydraulic lock situation is thus avoided.

The plunger spring may be arranged in a longitudinal bore in theconnecting rod and grounded at its distal end in the drive collar. Theproximal end of the plunger spring may bear against the proximal face ofthe cylinder from inside. Thus, the damper unit is arranged as a compactunit.

Preferably the arrangement for transferring a translation of a drivemeans to a plunger is applied in an auto-injector.

A reusable auto-injector for administering a dose of a liquid medicamentmay comprise:

-   -   an elongate housing arranged to contain the syringe with a        hollow needle and a stopper for sealing the syringe and        displacing the medicament, the housing having a distal end and a        proximal end with an orifice intended to be applied against the        injection site, wherein the syringe is slidably arranged with        respect to the housing, wherein a plunger is arranged for        transferring a translation to the stopper,    -   a drive spring capable of, upon activation:        -   pushing the needle from a covered position inside the            housing into an advanced position through the orifice and            past the proximal end, and        -   operating the syringe to supply the dose of medicament, and    -   activating means, i.e. the trigger button arranged to lock the        drive spring in a compressed state prior to manual operation and        capable of, upon manual operation, releasing the drive spring        for injection.

The elongate housing may comprise the distal portion and the proximalportion connected by a hinge, the hinge having a rotational axis offsetfrom a longitudinal axis of the auto-injector and oriented transversallywith respect to the longitudinal axis. The portions are rotatable aboutthe hinge relative to each other between an aligned position with theirlongitudinal axes aligned and a maximum opening angle. The drive springmay be compressed by rotating the portions out of the aligned positiontowards the maximum opening angle. The activating means are arranged tolock the drive spring in the compressed state when the portions arerotated at least almost by the maximum opening angle. A loading bay forholding the syringe is arranged in the proximal portion, the loading bayaccessible from its distal end for loading or unloading the syringe whenthe portions are rotated out of the aligned position, e.g. when they arerotated by least almost the maximum opening angle.

An alternative embodiment of the auto-injector may have the two portionsconnectable by other means than the hinge, e.g. a screw connection or abayonet fit.

When referring to the proximal and distal portion of the auto-injectorin this specification their respective distal and proximal ends arethose that point in the respective direction during an injection, i.e.with the portions aligned. In the terminology of this specification thedistal end of the distal portion remains the distal end even if theportions are rotated by the maximum opening angle in such a manner thatthe distal end of the distal portion essentially points in the samedirection as the proximal end of the proximal portion in this situation.

The said auto-injector is a reusable auto-injector, which may be splitin two by rotating the portions about the hinge. On the one hand thisrotating action serves for cocking the drive spring, on the other handit provides access to the loading bay in order to remove a spent syringeand insert a new, unused one. The auto-injector involves less useractions to reset it for another drug delivery compared to conventionalreusable auto-injectors. Conventional auto-injectors usually require theuser to dismantle it after use, load a new syringe, reset the drivespring and reassemble the auto-injector.

Once the activating means has been operated to release the drive springthe auto-injector will advance the syringe and needle thereby insertingthe needle into the injection site, e.g. a patient's skin. Furthermorethe auto-injector will automatically empty the syringe in order todeliver the medicament.

In a preferred embodiment a lever may be attached with one end to afixed first pivot in the proximal portion, wherein the other end of thelever may be attached to a second pivot arranged at a sliding shuttle inthe distal portion. The sliding shuttle may be translatable inlongitudinal direction of the distal portion between a maximum proximalposition when the portions are aligned and a maximum distal positionwhen the portions are rotated at least almost by the maximum openingangle, which may be about 180 degrees. A drive collar arranged at aproximal end of the drive spring may be engageable by the slidingshuttle in order to compress the drive spring, i.e. the sliding shuttlepushes the drive collar in a distal direction in the distal portion asthe portions are rotated out of alignment thus cocking the drive spring,whose distal end may be grounded inside the distal end of the distalportion. During that cocking process, the mechanical advantage increasesas the drive spring is compressed due to the lever action. This isparticularly advantageous if the drive means is a compression springwhose spring force increases with the level of compression. Thus, theuser effort required to reset the auto-injector is reduced.

In another preferred embodiment at least one interlock mechanism may bearranged, comprising first latch features for preventing the syringe andneedle from being pushed into the advanced position and furthercomprising second latch features for preventing a trigger button, i.e.the activating means from being pressed. The interlock mechanism servesfor defining an operation sequence of an auto-injector in a manner toallow a lateral trigger button to be operated only when a proximal endof the auto-injector is pressed against an injection site.

The interlock mechanism may be arranged to prevent the button from beingpressed as long as the auto-injector is not pressed against theinjection site in order to keep the user from activating theauto-injector inadvertently. This increases needle safety and reducesthe risk for needle stick injuries and for wasting the medicamentwithout injecting it. The first latch features and the second latchfeatures may be arranged to be disengaged by the proximal end of theauto-injector being pressed against an injection site. This skininterlock feature secures, that the device can only be triggered when itis properly positioned for an injection.

The skin interlock may comprise a detector sleeve arranged in theproximal portion and biased in proximal direction by a detector springinto a position with the detector sleeve protruding beyond the proximalend of the proximal portion. The interlock mechanism may be disengagedby pressing the detector sleeve against the injection site. Thus thedetector sleeve is translated against the force of the detector springin distal direction. The interlock mechanism may be arranged todisengage when the detector sleeve is pushed into the auto-injector andessentially on a level with the proximal end of the auto-injector.However, the interlock mechanism may also be arranged to disengage whenthe detector sleeve is pushed in and still protruding from the proximalend to a lesser extent than without being pushed.

Preferably the detector sleeve may comprise a longitudinal extension barextending at least almost to the distal end of the proximal portion whenthe detector sleeve is pushed into the auto-injector. The first latchfeature may comprise a dog and a syringe latch arm. The dog may protrudefrom the extension bar in a manner to disengage the syringe latch armfrom the loading bay when the detector sleeve is pushed into theauto-injector. Once the first latch feature is disengaged, the loadingbay with the syringe is allowed to be moved in proximal direction. Whenthe detector sleeve is not pushed into the auto-injector, the syringelatch arm prevents the syringe from being advanced.

The proximal end of the latch arm and/or the dog for engaging it maycomprise a ramp for easing their interaction.

The second latch features may comprise a dog arranged at the triggerbutton and a transmission bar arranged in the distal portion andslidable in longitudinal direction. A proximal end of the transmissionbar may bear against a distal end of the extension bar when the portionsare aligned. Consequently, translation of the detector sleeve isforwarded to the transmission bar when the portions are aligned. Arecess for the dog is provided in the transmission bar. When thedetector sleeve is not pushed into the auto-injector, the dog is blockedby the transmission bar. Hence, the trigger button cannot be pressed.Once the detector sleeve is pushed in, the dog may enter the recess thusallowing the trigger button to be pressed.

A detector means is arranged inside an elongate housing of theauto-injector at the proximal end. The detector means is slidable inlongitudinal direction and biased by a detector spring into a positionwith the detector means protruding beyond the proximal end. A dog isarranged at the trigger button. At least one longitudinal bar isprovided in the housing. At least one of the bars is slidable inlongitudinal direction and coupled to the detector means for jointmovement at least in distal direction.

The detector means may be arranged as an essentially tubular detectorsleeve or as a part with at least one tooth protruding beyond theproximal end.

The loading bay is preferably biased in distal direction by a syringeretraction spring. The syringe refraction spring may be a compressionspring arranged around the loading bay. It may be arranged to retractthe syringe in a manner to hide the needle inside the proximal portionafter delivering the dose of medicament by decoupling the plunger fromthe drive spring. This feature provides post-injection needle safety,i.e. the user is prevented from needle stick injury after removing theauto-injector from the injection site. The syringe spring may also beused to return the loading bay into the position where it is locked bythe first latch features when the housing is split into for replacingthe syringe.

The drive collar and the trigger button may be equipped with respectivesnap arms arranged to snap into each other when the drive spring issufficiently compressed. The snap arms may be disengaged by pressing thetrigger button.

Usually the hollow needle is equipped with a protective needle shieldfor keeping the needle sterile and preventing it from being mechanicallydamaged. The protective needle shield is attached to the needle when thesyringe is assembled.

In order to prepare the auto-injector for delivering a dose theprotective needle shield has to be removed from the needle.

In one embodiment of the invention a cap may be arrangeable at theproximal end of the proximal portion. In the cap barbs may be providedfor gripping the protective needle shield. When the cap is removed fromthe housing in preparation of an injection the protective needle shieldis reliably removed without exposing the user to too high a risk toinjure themselves.

The barbs may be arranged to snap into a circumferential notch or behinda shoulder of the protective needle shield.

Preferably the barbs are arranged to be constrained by the detectorsleeve from moving radially outward and inadvertently disengaging theprotective needle cap as long as the cap is attached to theauto-injector.

The cap may be attachable to the housing by a screw connection. Thisallows for a low force removal of the protective needle shield.

The housing may have at least one viewing window for inspecting thesyringe, or be manufactured from a transparent material.

The auto-injector may preferably be used for subcutaneous orintra-muscular injection, particularly for delivering one of ananalgesic, an anticoagulant, insulin, an insulin derivate, heparin,Lovenox, a vaccine, a growth hormone, a peptide hormone, a protein,antibodies and complex carbohydrates.

The term “medicament”, as used herein, means a pharmaceuticalformulation containing at least one pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a proteine, apolysaccharide, a vaccine, a DNA, a RNA, a antibody, an enzyme, anantibody, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exedin-3 or exedin-4 or an analogue or derivative ofexedin-3 or exedin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N—(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N—(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

-   H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,-   H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,-   des Pro36 [Asp28] Exendin-4(1-39),-   des Pro36 [IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or-   des Pro36 [Asp28] Exendin-4(1-39),-   des Pro36 [IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),-   wherein the group -Lys6-NH2 may be bound to the C-terminus of the    Exendin-4 derivative;-   or an Exendin-4 derivative of the sequence-   H-(Lys)6-des Pro36[Asp28] Exendin-4(1-39)-Lys6-NH2,-   des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,-   H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5des Pro36, Pro37, Pro38[Asp28] Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38[Asp28] Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38[Asp28] Exendin-4(1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36[Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,-   H-des Asp28 Pro36, Pro37, Pro38[Trp(O2)25] Exendin-4(1-39)-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38[Trp(O2)25, Asp28]    Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Trp(O2)25, Asp28]    Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38[Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38[Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36[Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,-   des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,-   H-(Lys)6-desPro36, Pro37, Pro38[Met(O)14, Asp28]    Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Met(O)14, Asp28]    Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38[Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38[Met(O)14, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5 des Pro36, Pro37, Pro38[Met(O)14, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-Lys6-des Pro36[Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-Lys6-NH2,-   H-des Asp28 Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25]    Exendin-4(1-39)-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38[Met(O)14, Asp28]    Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25, Asp28]    Exendin-4(S1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2;-   or a pharmaceutically acceptable salt or solvate of any one of the    afore-mentioned Exedin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

Further scope of applicability of the present invention will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating preferred embodiments of the invention, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will become more fully understood from thedetailed description given hereinbelow and the accompanying drawingswhich are given by way of illustration only, and thus, are not limitiveof the present invention, and wherein:

FIG. 1 is a longitudinal section of a reusable auto-injector,

FIG. 2 is a longitudinal section of the auto-injector during loading ofa syringe,

FIG. 3 is the auto-injector in a resetting step after loading,

FIG. 4 is the auto-injector during removal of a cap and a rigid needleshield,

FIG. 5 shows the cap and rigid needle shield in different stages ofoperation,

FIG. 6 is the auto-injector pressed against an injection site after thecap and rigid needle shields have been removed,

FIG. 7 is a perspective detail view of a syringe interlock with aprotective sleeve,

FIG. 8 is a perspective detail view of a trigger button interlock withthe protective sleeve,

FIG. 9 is the auto-injector during actuation by means of the triggerbutton,

FIG. 10 is a perspective detail view of a loading bay,

FIG. 11 is another perspective detail view of the loading bay,

FIG. 12 is the auto-injector near the end of an injection stroke,

FIG. 13 is a detail view of a damped delay member near the end of theinjection stroke,

FIG. 14 is a detail view of the damped delay member decoupled from thesyringe after the end of the injection,

FIG. 15 is a perspective view of the damped delay member of FIG. 13,

FIG. 16 is a perspective view of the damped delay member of FIG. 14,

FIG. 17 is the auto-injector when being removed from the injection site,and

FIG. 18 is the auto-injector during removal of the spent syringe.

Corresponding parts are marked with the same reference symbols in allfigures.

DETAILED DESCRIPTION

FIG. 1 is a longitudinal section of a reusable auto-injector 1. Theauto-injector 1 comprises an elongate housing 2. A disposable syringe 3,e.g. a Uni-Life syringe, with a hollow needle 4 is arranged in aproximal portion of the auto-injector 1. When the syringe 3 is assembleda protective needle shield 5 is attached to the needle 4. A stopper 6 isarranged for sealing the syringe 3 distally and for displacing a liquidmedicament M through the hollow needle 4. The syringe 3 is held in atubular loading bay 7. A drive spring 8 in the shape of a compressionspring is arranged in a distal portion of the auto-injector 1. A plunger9 is arranged for forwarding the spring force of the drive spring 8. Thedrive spring 8 is used for providing axial motion for advancing thesyringe 3, inserting the needle 4 into the injection site, i.e. apatient's skin and injecting a dose of medicament M.

In the present embodiment the needle 4 is withdrawn into the syringe 3once fully emptied. However, a post-injection needle safety function maybe alternatively integrated into the auto-injector 1 instead of thesyringe 3.

The elongate housing 2 comprises an essentially tubular distal portion2.1 and an essentially tubular proximal portion 2.2 connected by a hinge10 so the portions 2.1, 2.2 may be operated similar to a break barrelair rifle.

FIG. 2 shows how the disposable syringe is loaded into the auto-injector1. The housing 2 is breached around the hinge 10 so the portions 2.1,2.2 are not aligned any more. The syringe 3 may now be inserted into theloading bay 7 through the distal opening of the proximal portion 2.2. Alever 11 is attached with one end to a fixed first pivot 12 in theproximal portion 2.2 of the housing 2. The other end of the lever 11 isattached to a second pivot 13 arranged at a sliding shuttle 14 in thedistal portion 2.1, the sliding shuttle 14 moveable in longitudinaldirection. When the portions 2.1, 2.2 are aligned as in FIG. 1 thesliding shuttle 14 is held in a maximum proximal position by the lever11. When the housing 2 is breached around the hinge as in FIG. 2 thelever 11 forces the sliding shuttle 14 to move in distal direction D asshown in FIG. 2. In FIG. 2 the drive spring 8 is already in a compressedstate. However, if the auto-injector 1 is breached open following aninjection the then relaxed drive spring 8 is cocked by the lever 11since the sliding shuttle 14 bears against a drive collar 15 arranged ata proximal end of the drive spring 8 (cf. FIG. 18). When the slidingshuttle 14 has pushed the drive collar 15 to a maximum distal position asnap arm 15.1 of the drive collar snaps behind a snap arm 16.1. of atrigger button 16. This lever action resets the auto-injector 1 foranother injection cycle.

After cocking the drive spring and inserting the syringe 3 in the mannerdescribed the user closes the auto-injector 1 by rotating the distalportion 2.1 about the hinge 10 until its longitudinal axis is aligned tothe longitudinal axis of the proximal portion 2.2 as shown in FIG. 3. Asthe auto-injector 1 is closed, the sliding shuttle 14 translates inproximal direction P within the distal portion 2.1. A locking mechanism(not illustrated) may be provided for locking the two portions 2.1, 2.2in a coaxial position. An example mechanism may comprise a cylindricalsleeve mounted around the external surface of the housing 2 constrainedto translate along the longitudinal axis. To lock the auto-injector 1,once the syringe 3 had been loaded, the sleeve may be positioned acrossthe joint between the distal portion 2.1 and the proximal portion 2.2thereby preventing rotation about the hinge 10. The sleeve may be sprungloaded such that it automatically locks the portions 2.1, 2.2 coaxiallyupon aligning them.

In FIG. 4 the auto-injector 1 is shown during removal of a cap 17 whichhad been attached to a proximal end P of the proximal portion 2.2. Barbs17.1 on the cap (see FIG. 5 a, b) constrained from moving outward by adetector sleeve 18 slidably arranged at the proximal end P inside theproximal portion 2.2 grip the protective needle shield 5 thus removingthe protective needle shield 5 with the cap 17. Once the cap 17 isremoved, the barbs 17.1 are no longer constrained so the protectiveneedle shield 5 is released and may be easily removed from the cap 5(see FIG. 5 c).

FIGS. 6, 7 and 8 show details of an interlock mechanism for defining asequence of operation of the auto-injector 1.

Following the removal of the cap 17 the user places the proximal end ofthe auto-injector 1 against an injection site, i.e. the user's skin.This causes the detector sleeve 18 to translate in distal directionagainst the bias of a detector spring 19 (see FIG. 6). As the detectorsleeve 17 translates, first latch features and second latch features arereleased. The first and second latch features prevent the user fromaccidentally actuating the auto-injector 1 when it is not in contactwith the injection site and during a loading and cocking step.

The first latch features comprise a syringe latch arm 20 transversallypivoted about halfway between its ends, the distal end having a nose20.1 for engaging behind a shoulder 7.1 arranged at the loading bay 7 ina manner to prevent the loading bay 7 from being moved in proximaldirection P (see FIG. 7 for details). The proximal end of the syringelatch arm 20 comprises a ramp 20.2. The detector sleeve 18 comprises alongitudinal extension bar 18.1 extending at least almost to the distalend of the proximal portion 2.2 when the detector sleeve 18 is pushedinto the auto-injector 1 and essentially on a level with the proximalend P. A dog 18.2 protrudes inwardly from the extension bar 18.1 in amanner to engage the ramp 20.2 when the detector sleeve 18 is pushedinto the auto-injector 1, thereby pushing the proximal end of thesyringe latch arm 20 inwardly and the distal end of the syringe latcharm 20 outwardly so the nose 20.1 is disengaged from the shoulder 7.1.Thus the loading bay 7 is no longer constrained from being moved inproximal direction P. As long as the detector sleeve 18 is not pushedback the dog 18.2 does not interact with the ramp 20.2. A spring may bearranged for keeping the nose 20.1 engaged with the shoulder 7.1 in thissituation (not illustrated).

In another embodiment the latch arm 20 may have a straight end insteadof the ramp in which case a ramp may be provided at the dog 18.2. In yetanother embodiment both the latch arm 20 and the dog 18.2 may haveramps.

The second latch features are part of a transmission bar 21 arranged inthe distal portion 2.1 and slidable in longitudinal direction. When theportions 2.1, 2.2 are coaxially aligned a proximal end of thetransmission bar 21 bears against a distal end of the extension bar18.1. For this purpose the transmission bar 21 may be biased by a springin proximal direction (not illustrated). Near a distal end of thetransmission bar 21 a recess 21.1 is provided for engaging a dog 16.2arranged at the trigger button 16 (see FIG. 8 for details). Before thedetector sleeve 18 is pushed into the auto-injector 1 (cf. FIG. 1) thetransmission bar 21 is in a proximal position thus engaging the dog 16.2in a manner to prevent the trigger button 16 from being pushed inwardlyat its proximal end. The distal end of the trigger button 16 is pivotedin the distal portion 2.1. When the detector sleeve 18 is pushed intothe auto-injector 1 the translation is forwarded by the extension bar18.1 to the transmission bar 21 so the dog 16.2 of the trigger button 16finds some clearance in the recess 21.1 thus allowing the proximal endof the trigger button 16 to be pushed inward.

In order to deliver an injection the user depresses the trigger button16. As the proximal end of the trigger button 16 moves inward the snaparms 15.1, 16.1 disengage thus releasing the drive collar 15 andallowing the drive spring 8 to extend. The force from the drive spring 8is transferred through the drive collar 15 and a release latch member 22to the plunger 9. The friction between the stopper 6 and the inner wallof the syringe 3 opposes relative motion between them. This friction isgreater than a sum of the force of a syringe retraction spring 23arranged between the shoulder 7.1 of the loading bay 7 and a protrusion24 in the proximal portion 2.2 and a needle insertion force between theneedle 4 and the patient's skin. Hence the needle 4 is inserted into theuser's skin without medicament leaking out of the needle's tip (wetinjection). An insertion depth is controlled by a finger flange orshoulder 7.1 of loading bay 7 contacting a stop 25 arranged in theproximal portion 2.2 (see FIGS. 10 and 11). The stop 25 or the two stops25 may be arranged at a proximal end of a respective longitudinal rib25.1 arranged in the proximal portion 2.2. The loading bay flange 7.1may have recesses for rotationally fixing the loading bay flange 7.1 bythe longitudinal ribs 25.1.

Once the finger flange 3.1 contacts the stops 25, the force of the drivespring 8 acting on the stopper 6 is sufficient to overcome friction sothe emptying of the syringe contents commences.

The drive collar 15 is coupled to the release latch member 22 through adamper unit 26 comprising a plunger spring 26.1 in parallel with aviscous damper 26.2. A coefficient of damping of the viscous damper 26.2is specified such that a time taken to fully compress the plunger spring26.1 is greater than a time required to fully empty the syringe 3. Thismeans the stopper 6 will always fully empty the syringe 3.

In the FIGS. 15 and 16 the damper unit 26 is shown in detail. Theviscous damper 26.2 comprises a piston 26.2.1 fixed to the drive collar15 by a connecting rod 26.2.2, the piston 26.2.1 having a greaterdiameter than the connecting rod 26.2.2. A hollow cylinder 26.2.3 withan internal diameter slightly greater than the diameter of the piston26.2.1 is arranged around the piston 26.2.1 so the piston 26.1.1 andcylinder 26.2.3 may reciprocate. A proximal end face of the cylinder26.2.3 is fully closed. A distal end face is arranged to seal thecylinder 26.2.3 against the connecting rod 26.2.2. A small transfer port26.2.4 is provided through the piston 26.2.1 in longitudinal directionallowing a fluid to flow from the distal side of the piston 26.2.1 tothe proximal side and vice versa. Respective gasket rings 26.2.5 and26.2.6 are arranged to seal the piston 26.2.1 against the cylinder26.2.3 and the connecting rod 26.2.2 against the hole in the distal endface of the cylinder 26.2.3. The piston 26.2.1 and the distal face wallare provided with respective circumferential notches in order to holdthe gasket rings 26.2.5, 26.2.6 in place. There may be more than onetransfer port 26.2.4 through the piston 26.2.1. The size of the transferport 26.2.4 controls the damper characteristics. The fluid may be one ofair, another gas, a liquid, grease, e.g. silicone grease. If anincompressible fluid, such as a liquid is used, an air pocket may beprovided in the cylinder 26.2.3 in order to compensate for the disparityin volume change at the proximal and the distal side of the piston26.2.1 during translation.

The plunger spring 26.1 is arranged in a longitudinal bore in theconnecting rod 26.2.2 and grounded at its distal end in the drive collar15. The proximal end of the plunger spring 26.1 bears against theproximal face of the cylinder 26.2.3 from inside. Hence the cylinder26.2.3 may be translated towards the drive collar 15 against the forceof the plunger spring 26.1 and the plunger spring 26.1 may push thecylinder 26.2.3. away from the drive collar 15.

The release latch member 22 is distally pivoted in the damper unit 26,particularly in the cylinder 26.2.3.

Once the syringe 3 is fully emptied and the plunger spring 26.1 is fullycompressed, a ramp 15.2 on the drive collar 15 contacts a ramp 22.1 onthe release latch member 22 thus rotating the release latch member 22outward and consequently decoupling the drive spring 8 from the plunger9 (see FIGS. 14 and 16). The needle 4 is withdrawn inside the syringe 3.This may be achieved by the stopper 6 gripping the distal end of theneedle 4. The stopper 6 may be pulled in distal direction by means of aspring arranged inside the syringe 3 (not illustrated in the figures).The needle 4 is thus pulled into the syringe 3 and the plunger 9 pushedout in distal direction D into the gap vacated by the latch member. Inorder to enable both the withdrawal of the needle 4 and the syringe 3sufficient space has to be provided for the distal end of the plunger 9towards the damper unit 26. This is achieved by appropriately selectingthe length of the release latch member 22. Due to the interrupted forcepropagation the plunger spring 26.1 will return the cylinder 26.2.3 toits initial position for further injections as shown in FIGS. 12 and 15.

The lever action described above is reversed, i.e. the distal portion2.1 is rotated about the hinge 10 with respect to the proximal portion2.2 thus allowing access to the loading bay 7 (see FIG. 18). As theauto-injector 1 is hinged in two, the lever 11 translates the slidingshuttle 14 in distal direction of the distal portion 2.1. The slidingshuttle 14 contacts the drive collar 15 and compresses the drive spring8 in preparation for further injections.

Upon full opening, the snap arms 15.1 and 16.1 of the drive collar 15and the trigger button 16 snap into each other thus preventing the drivespring 8 from expanding. The emptied syringe 3 may now be safely removedfrom the loading bay 7.

The damper unit 26 may now return to its initial state under the forceof the plunger spring 26.1.

The detector sleeve 18 is pushed in proximal direction P of the proximalportion 2.2 under load of the compressed detector spring 19. Thedetector spring 19 may be grounded in the protrusion 24.

Although the figures illustrate a syringe 3 with a retracting needle,which ensures needle safety at all times even when changing thedisposable syringe, the auto-injector 1 would also work with a fixedneedle syringe, such as a Hypak syringe as well.

The invention claimed is:
 1. An injection device, comprising a syringewith a hollow needle and a stopper for sealing the syringe anddisplacing a medicament (M) stored in the syringe, the injection devicefurther comprising a drive means, a plunger arranged for pushing againstthe stopper and an arrangement for transferring a translation of thedrive means to the plunger, wherein the arrangement comprises anelongate release latch member pivoted at one end which is connected toeither the drive means or the plunger, the release latch member havinganother end for engaging the respective other one of the drive means orthe plunger, wherein the release latch member is arranged to have itsnon-pivoted other end disengaged by rotation due to contact between atleast one ramp and another component when the stopper has at leastnearly displaced all of a predefined dose of the medicament (M), whereina length of the release latch member is specified so as to provide aclearance between the plunger and the drive means when the release latchmember is engaged in order to allow at least the plunger, the stopperand the hollow needle to be retracted at least far enough to hide theneedle inside the syringe or inside a housing after disengaging therelease latch member, wherein the release latch member is arranged to bedisengaged depending on a distance travelled until at least all of thepredefined dose has been delivered, wherein the release latch member isarranged to be disengaged depending on a time elapsed from a beginningof the translation, wherein a damper unit is arranged in series with thedrive means and the release latch member, the damper unit comprising aviscous damper, and wherein the viscous damper comprises a piston fixedto a drive collar by a connecting rod, the drive collar being arrangedat a proximal end of the drive means, the piston having a greaterdiameter than the connecting rod, wherein a hollow cylinder with aninternal diameter slightly greater than the diameter of the piston isarranged around the piston thus allowing the piston and cylinder toreciprocate, wherein a proximal end face of the cylinder is fully closedand wherein a distal end face of the cylinder is arranged to seal thecylinder against the connecting rod, wherein at least one transfer portis provided through the piston in a manner to allow a fluid to flowbetween the distal side of the piston and the proximal side.
 2. Theinjection device according to claim 1, wherein the damper unit comprisesa plunger spring, wherein a coefficient of damping of the damper isspecified such that a time taken to fully compress the plunger spring isgreater than a time required to displace the predefined dose.
 3. Theinjection device according to claim 1, wherein the medicament stored inthe syringe equals the predefined dose.
 4. The injection deviceaccording to claim 1, wherein at least one gasket ring is arranged toseal the piston against the cylinder and/or the connecting rod againstthe distal end face of the cylinder.
 5. The injection device accordingto claim 1, wherein the plunger spring is arranged in a longitudinalbore in the connecting rod and grounded at its distal end in the drivecollar, wherein the proximal end of the plunger spring bears against theproximal face of the cylinder from inside.
 6. The injection deviceaccording to claim 1 arranged as an auto-injector (1) for administeringa dose of a liquid medicament (M), comprising: an elongate housingarranged to contain the syringe with the hollow needle and the stopperfor sealing the syringe and displacing the medicament (M), the housinghaving a distal end (D) and a proximal end (P) with an orifice intendedto be applied against an injection site, wherein the syringe is slidablyarranged with respect to the housing, wherein the plunger is arrangedfor forwarding a translation to the stopper, the drive means in theshape of a drive spring capable of, upon activation: pushing the needlefrom a covered position inside the housing into an advanced positionthrough the orifice and past the proximal end (P), and operating thesyringe to supply the dose of medicament (M), and trigger assemblyarranged to lock the drive spring in a compressed state prior to manualoperation and capable of, upon manual operation, releasing the drivespring for injection, the elongate housing comprising a distal portionand a proximal portion connected by a hinge, the portions rotatableabout the hinge relative to each other between an aligned position and amaximum opening angle, wherein the drive spring is compressed byrotating the portions out of the aligned position towards the maximumopening angle, wherein the trigger assembly is arranged to lock thedrive spring in the compressed state when the portions are rotated atleast almost to the maximum opening angle and wherein a loading bay forholding the syringe is arranged in the proximal portion, the loading baybeing accessible from its distal end for loading or unloading thesyringe when the portions are rotated out of the aligned position. 7.The injection device according to claim 6, wherein a lever is attachedwith one end to a fixed first pivot in the proximal portion, wherein theother end of the lever is attached to a second pivot arranged at asliding shuttle in the distal portion, the sliding shuttle translatablein longitudinal direction of the distal portion between a maximumproximal position when the portions are aligned and a maximum distalposition when the portions are rotated at least almost by the maximumopening angle, wherein the drive collar is engageable by the slidingshuttle in order to pressurize the drive spring.
 8. The injection deviceaccording to claim 6, wherein at least one interlock mechanism isarranged, comprising first latch features for preventing the syringe andneedle from being pushed into the advanced position, further comprisingsecond latch features for preventing a trigger button from beingpressed, wherein the first latch features and the second latch featuresare disengageable by the proximal end (P) of the auto-injector beingpressed against an injection site.
 9. The injection device according toclaim 8, wherein a detector sleeve is arranged in the proximal portionand biased in proximal direction (P) by a detector spring into aposition with the detector sleeve protruding beyond the proximal end (P)of the proximal portion, wherein the interlock mechanism isdisengageable by pressing the detector sleeve against the injectionsite.
 10. The injection device according to claim 9, wherein thedetector sleeve comprises a longitudinal extension bar extending atleast almost to the distal end of the proximal portion when the detectorsleeve is pushed into the auto-injector, wherein the first latchfeatures comprise a dog and a syringe latch arm, the dog protrudinginwardly from the extension bar in a manner to disengage the syringelatch arm from the loading bay when the detector sleeve is pushed intothe auto-injector thus allowing the loading bay with the syringe to bemoved in proximal direction (P), wherein the syringe latch arm isarranged to prevent the syringe from being advanced when not disengagedfrom the loading bay by the dog.
 11. The injection device according toclaim 10, wherein the second latch features comprise a dog arranged atthe trigger button and a transmission bar arranged in the distal portionand slidable in longitudinal direction, wherein a proximal end of thetransmission bar bears against a distal end of the extension bar whenthe portions are aligned, wherein a recess for the dog is provided inthe transmission bar for allowing the trigger button to be pressed whenthe detector sleeve is being pushed into the injection device autoinjector and wherein otherwise the dog is engaged with the transmissionbar in a manner to prevent the trigger button from being pressed.